The effects of head injury on expression of neurotrophic factors and receptors for neurotrophic factors will be examined, and mechanisms responsible for injury-related changes in expression of these proteins will be characterized. The effects, on response to experimental brain injury, of experimentally altered expression of neurotrophic factors, will be examined. Specific immunoassays will be employed to monitor the appearance of neurotrophic factors (nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, basic fibroblast growth factor) in spinal fluid of human head injury patients. Another approach will use an experimental model of closed head injury in rats. After injury, appearance of neurotrophic factors in spinal fluid will be monitored, and immunocytochemical and in situ hybridization techniques will be employed to localize sites of altered expression of neurotrophic factors and their receptors subsequent to injury. The involvement of interleukin-1 in mediating effects of head injury on neurotrophic factor expression will be assessed in rats by intraventricular injection of IL-1, and by exposure of hippocampal slice preparations to IL-1. The ability of enhanced expression of neurotrophic factors to promote functional recovery after head injury will be assessed in rats and mice. The effects of intraventricular infusion of NGF on functional recovery following closed head injury in rats will be examined. Transgenic mice with enhanced expression of bFGF or NGF will be tested for improved recovery following surgical and neurotoxic brain lesions. These studies will characterize whether neurotrophic factors normally play a role in functional recovery following severe head injuries, and will determine whether manipulation of neurotrophic factor availability can promote functional recovery in animal models of human head injury. Such studies may suggest ways in which management of neurotrophic factor status might promote functional recovery from human head injuries of diverse types. This project is related to the projects of Dr. Reh and Dr. Westrum in addressing basic mechanisms influencing neural plasticity as it relates to recovery from head injury and is related to the project of Dr. Grady in examining functional roles of NGF in head injury.